- PDB-6o3l: Crystal structure of the Fab fragment of the human HIV-1 neutrali... -
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基本情報
登録情報
データベース: PDB / ID: 6o3l
タイトル
Crystal structure of the Fab fragment of the human HIV-1 neutralizing antibody PGZL1.H4K3 in complex with its MPER peptide epitope (region 671-683 of HIV-1 gp41).
要素
MPER peptide, region 671-683 of HIV-1 gp41
PGZL1.H4K3 heavy chain
PGZL1.H4K3 light chain
キーワード
IMMUNE SYSTEM / PGZL1 ANTI HIV-1 / GP41 MPER / MEMBRANE LIPIDS / BROADLY NEUTRALISING HIV-1 ANTIBODY
機能・相同性
機能・相同性情報
Synthesis and processing of ENV and VPU / evasion of host immune response / Alpha-defensins / Dectin-2 family / Binding and entry of HIV virion / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / actin filament organization ...Synthesis and processing of ENV and VPU / evasion of host immune response / Alpha-defensins / Dectin-2 family / Binding and entry of HIV virion / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / actin filament organization / Assembly Of The HIV Virion / Budding and maturation of HIV virion / clathrin-dependent endocytosis of virus by host cell / viral protein processing / symbiont entry into host cell / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / structural molecule activity / virion membrane / membrane 類似検索 - 分子機能
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
UM1 AI100663
米国
引用
ジャーナル: Nat Commun / 年: 2019 タイトル: An MPER antibody neutralizes HIV-1 using germline features shared among donors. 著者: Lei Zhang / Adriana Irimia / Lingling He / Elise Landais / Kimmo Rantalainen / Daniel P Leaman / Thomas Vollbrecht / Armando Stano / Daniel I Sands / Arthur S Kim / / Pascal Poignard / ...著者: Lei Zhang / Adriana Irimia / Lingling He / Elise Landais / Kimmo Rantalainen / Daniel P Leaman / Thomas Vollbrecht / Armando Stano / Daniel I Sands / Arthur S Kim / / Pascal Poignard / Dennis R Burton / Ben Murrell / Andrew B Ward / Jiang Zhu / Ian A Wilson / Michael B Zwick / 要旨: The membrane-proximal external region (MPER) of HIV-1 envelope glycoprotein (Env) can be targeted by neutralizing antibodies of exceptional breadth. MPER antibodies usually have long, hydrophobic ...The membrane-proximal external region (MPER) of HIV-1 envelope glycoprotein (Env) can be targeted by neutralizing antibodies of exceptional breadth. MPER antibodies usually have long, hydrophobic CDRH3s, lack activity as inferred germline precursors, are often from the minor IgG3 subclass, and some are polyreactive, such as 4E10. Here we describe an MPER broadly neutralizing antibody from the major IgG1 subclass, PGZL1, which shares germline V/D-region genes with 4E10, has a shorter CDRH3, and is less polyreactive. A recombinant sublineage variant pan-neutralizes a 130-isolate panel at 1.4 μg/ml (IC). Notably, a germline revertant with mature CDR3s neutralizes 12% of viruses and still binds MPER after DJ reversion. Crystal structures of lipid-bound PGZL1 variants and cryo-EM reconstruction of an Env-PGZL1 complex reveal how these antibodies recognize MPER and viral membrane. Discovery of common genetic and structural elements among MPER antibodies from different patients suggests that such antibodies could be elicited using carefully designed immunogens.